Drug-eluting balloon: Very short-term exposure and overlapping

Bodo Cremers; Ulrich Speck; Nicola Kaufels; Dirk Mahnkopf; Michael Kühler; Michael Böhm; Bruno Scheller

doi:10.1160/TH08-06-0387

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 2009; 101(01): 201-206
DOI: 10.1160/TH08-06-0387

New Technologies, Diagnostic Tools and Drugs

Schattauer GmbH

Drug-eluting balloon: Very short-term exposure and overlapping

Authors

Bodo Cremers

¹University of Saarland, Homburg/Saar, Department of Internal Medicine III, Germany
Ulrich Speck

²Humboldt University Berlin, Campus Charité Mitte, Department of Radiology, Germany
Nicola Kaufels

²Humboldt University Berlin, Campus Charité Mitte, Department of Radiology, Germany
Dirk Mahnkopf

³IMTM GmbH, Immune Technologies & Medicine, Rottmersleben, Germany
Michael Kühler

⁴B. Braun Melsungen AG, Vascular Systems, Berlin, Germany
Michael Böhm

¹University of Saarland, Homburg/Saar, Department of Internal Medicine III, Germany
Bruno Scheller

¹University of Saarland, Homburg/Saar, Department of Internal Medicine III, Germany

Abstract

Summary

Paclitaxel balloon coating has shown promising effects in inhibiting restenosis in initial clinical trials. The aim of the present study was to evaluate the influence of two critical features of drug-eluting balloon (DEB) application – inflation time and increased dose due to overlapping balloons. Fifty-six stainless steel stents were implanted in the left anterior descending and circumflex coronary arteries of 28 domestic pigs using a 1.2:1.0 overstretch ratio. Stents were mounted on conventional un-coated and paclitaxel-coated angioplasty balloon catheters. The animals were randomized to five different treatments with a range of short (10 seconds [s] inflation using 1 DEB) to extended (2x60 s inflation using 2 DEB) intima contact time. After 28 days, quantitative angiography and histomorphometry of the stented arteries was performed on a total of 23 pigs. Paclitaxel balloon coating led to a marked reduction of parameters characterizing in-stent stenosis: Late lumen loss was 1.37 ± 0.49 mm for uncoated balloons, 0.23 ± 0.42 mm for one coated balloon 60 s inflation time, 0.37 ± 0.28 mm for 10 s inflation time and 0.30 ± 0.19 mm for the vessel segment treated by two coated balloons with 60 s inflation each. Neointimal areas were 4.26 ± 1.18, 1.68 ± 0.23, 1.83 ± 0.40 and 1.67 ± 0.46 mm², respectively (p=0.001 versus control, p>0.05 between paclitaxel-treated groups). Despite the marked reduction of neointimal proliferation, endothelialization of stent struts was present in all samples. DEB were found to effectively reduce neointimal proliferation regardless of inflation time and dose within the tested range. No adverse reactions were seen as dose was increased to more than three times the clinically tested dose.

Keywords

Restenosis - drug-eluting balloon - inflation time - overlap - paclitaxel

Full Text

References

References
1 Heldman AW, Cheng L, Jenkins GM. et al. Paclitaxel stent coating inhibits neointimal hyperplasia at 4 weeks in a porcine model of coronary restenosis. Circulation 2001; 103: 2289-2295.
2 Morice MC, Serruys PW, Sousa JE. et al. A randomized comparison of a sirolimus-eluting stent with a standard stent for coronary revascularization. N Engl J Med 2002; 346: 1773-1780.
3 Fattori R, Tommaso P. Drug-eluting stents in vascular intervention. Lancet 2003; 361: 247-249.
4 Stone GW, Ellis SG, Cox DA. et al. A polymer-based, paclitaxel-eluting stent in patients with coronary artery disease. N Engl J Med 2004; 350: 221-231.
5 Iofina E, Langenberg R, Blindt R. et al. Polymer-based paclitaxel-eluting stents are superior to non-polymer-based paclitaxel-eluting stents in the treatment of de novo coronary lesions. Am J Cardiol 2006; 98: 1022-1027.
6 Maisel WH. Unanswered questions. Drug-eluting stents and the risk of late thrombosis. N Engl J Med 2007; 356: 981-984.
7 Mori T, Kinoshita Y, Watanabe A. et al. Retention of paclitaxel in cancer cells for 1 week in vivo and in vitro. Cancer Chemother Pharmacol 2006; 58: 665-672.
8 Scheller B, Speck U, Romeike B. et al. Contrast media as carriers for local drug delivery. Successful inhibition of neointimal proliferation in the porcine coronary stent model. Eur Heart J 2003; 24: 1462-1467.
9 Scheller B, Speck U, Schmitt A. et al. Addition of paclitaxel to contrast media prevents restenosis after coronary stent implantation. J Am Coll Cardiol 2003; 42: 1415-1420.
10 Scheller B, Speck U, Abramjuk C. et al. Paclitaxel balloon coating, a novel method for prevention and therapy of restenosis. Circulation 2004; 110: 810-814.
11 Speck U, Scheller B, Abramjuk C. et al. Neointima inhibition: comparison of effectiveness of non-stent-based local drug delivery and a drug-eluting stent in porcine coronary arteries. Radiology 2006; 240: 411-418.
12 Scheller B, Hehrlein C, Bocksch W. et al. Treatment of coronary in-stent restenosis with a paclitaxel-coated balloon catheter. N Engl J Med 2006; 355: 2113-2124.
13 Schwartz RS, Huber KC, Murphy JG. et al. Restenosis and the proportional neointimal response to coronary artery injury: results in a porcine model. J Am Coll Cardiol 1992; 19: 267-274.
14 Kornowski R, Hong MK, Tio FO. et al. In-stent restenosis: contributions of inflammatory responses and arterial injury to neointimal hyperplasia. J Am Coll Cardiol 1998; 31: 224-230.
15 Axel DI, Kunert W, Goggelmann C. et al. Paclitaxel inhibits arterial smooth muscle cell proliferation and migration in vitro and in vivo using local drug delivery. Circulation 1997; 96: 636-645.
16 Hwang CW, Wu D, Edelman ER. Physiological transport forces govern drug distribution for stent-based delivery. Circulation 2001; 104: 600-605.
17 Lansky AJ, Costa RA, Mintz GS. et al. Non-polymer-based paclitaxel-coated coronary stents for the treatment of patients with de novo coronary lesions: angiographic follow-up of the DELIVER clinical trial. Circulation 2004; 109: 1948-1954.
18 Schwartz RS, Edelman ER, Carter A. et al. Preclinical evaluation of drug-eluting stents for peripheral applictions: recommendations from an expert consensus group. Circulation 2004; 110: 2498-2505.
19 Carter AJ, Aggarwal M, Kopia GA. et al. Longterm effects of polymer-based, slowrelease, sirolimus-eluting stents in a porcine coronary model. Cardiovasc Res 2004; 63: 617-624.
20 Farb A, Heller PF, Shroff S. et al. Pathological analysis of local delivery of paclitaxel via a polymer-coated stent. Circulation 2001; 104: 473-479.
21 Dommke C, Haase KK, Süselbeck T. et al. Local paclitaxel delivery after coronary stenting in an experimental animal model. Thromb Haemost 2007; 98: 674-680.